Research from the Fred Hutchinson Cancer Center and the University of Washington (UW) have discovered that different combinations of medications can significantly lower blood pressure in patients who receive the cancer drug ibrutinib. The research, published in the journal Blood Advances, notes that patients receiving ibrutinib and other drugs in its class often develop new or worsening high blood pressure of hypertension.
Ibrutinib was the first Bruton tyrosine kinase inhibitor (BTKi) approved by the FDA in 2013 for the treatment of lymphatic cancers. Three other BTKis have been approved since then: acalabrutinib in 2017, zanubrutinib in 2019, and pirtobrutinib in 2023.
While hypertension is known as a serious side effect of these targeted treatments, due to the relative newness of this class of drugs few studies have sought to find the best methods of treating it, and there are currently no formal treatment guidelines doctors can rely upon to treat patients who develop it.
“To our knowledge, this is the first and only study to examine how to optimally treat high blood pressure in patients receiving ibrutinib,” said the study’s senior author Mazyar Shadman, MD, of Fred Hutchinson Cancer Center and the UW School of Medicine. “Our findings strongly suggest that aggressive treatment with certain combinations of antihypertensive medications can achieve significantly reduced blood pressures in this patient population.”
For this study, Shadman, first author Laura Samples, MD, also of Fred Hutchinson Cancer Center and UW School of Medicine, and colleagues studied the records of 196 patients who received one or more hypertensive medication for at least three months while they were also being treated with ibrutinib. The study was conducted between 2014 and 2018 with participation from 14 medical centers in the U.S. The patient breakdown was nearly 93% Caucasian, 71% male, 29% female, with an average age of 67 years. The patients were divided into two groups: those who were taking at least one hypertensive medication before starting BTKi treatment (118), and those who began taking one or more hypertensive medication who developed new onset high blood pressure after starting BTKi therapy (78).
The antihypertensive medications were from four different classes of drugs: ACE inhibitors and angiotensin receptor blockers (ARBs), beta blockers, calcium channel blockers, and hydrochlorothiazide. The study’s primary outcome was how effective the antihypertensive treatments were as measured by average reduction mean arterial pressure (MAP), which is the average pressure in a patient arteries during one heartbeat cycle.
Patients who had hypertension prior to treatment showed a statistically significant reductions in MAP when taking beta blockers in combination with hydrochlorothiazide. Patients with new-onset hypertension after commencing ibrutinib treatments who were treated with ACE inhibitors and ARBs in combination with hydrochlorothiazide showed similar reductions.
Significantly, 15% of patients from both groups taking beta blockers and hydrochlorothiazide what was classified at normal blood pressure—in the range of 120/80 or lower.
“Our results reinforce that—in this patient population as in patients with hypertension in general—you need to treat with multiple drugs to achieve successful blood pressure control,” Samples said.
The researchers noted that these findings do not provide information on why particular combinations of antihypertensive drugs achieved these reductions, but the data may provide a window for other researchers to make further determinations. The team also noted that a limitation of the research is that it was a retrospective study and that large prospective studies should be conducted to develop any formal guidelines for how to treat patients with hypertension who are receiving BTKis.
Future studies should also find ways to leverage remote blood pressure devices that can capture data from a 24-hour period. Blood pressure data was solely from measurements taken in the clinic and previous studies have shown blood pressure checks in different clinical setting show varied results.
